A new multicompartmental reaction-diffusion modeling method links transient membrane attachment of E. coli MinE to E-ring formation.
A new multicompartmental reaction-diffusion modeling method links transient membrane attachment of E. coli MinE to E-ring formation.
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DOI：
10.1007/s11693-009-9047-2
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发表时间：
2010-03-01
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通讯作者：
Tomita, Masaru
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作者：
Arjunan, Satya Nanda Vel;Tomita, Masaru
未标记：许多重要的细胞过程受细胞质和膜上发生的分子反应扩散 (RD) 的调节。为了对此类多室过程进行建模和分析，我们开发了一种基于格的蒙特卡罗方法 SpatiCell，该方法支持单分子分辨率下体积和表面室中的 RD。 RD 的随机性和细胞内分子拥挤带来的排除体积效应，两者都可以显着影响 RD，从而影响细胞过程。我们通过将扩散、不可逆和可逆反应的模拟结果与预测的解析和最佳可用数值解进行比较来验证该方法。此外，为了直接将荧光显微镜图像中分子的定位模式与模拟进行比较，我们设计了一种可视化方法，通过显示根据相机曝光时间平均的模拟分子轨迹来模拟显微摄影过程。在杆状细菌大肠杆菌中，分裂位点在细胞极受到 Min 蛋白（MinC、MinD 和 MinE）周期性极间振荡的抑制，这种振荡是由细胞质和膜区室中精心策划的 RD 产生的。使用 Spatiitive，我们可以通过考虑先前报道的 MinE 特性来建模和重现体内 MinDE 定位动态。我们的结果表明，对于防止极性分隔至关重要的 MinE 环主要由 MinE 组成，MinE 在被 MinD 招募后短暂独立地附着在膜上。总体而言，Spatiitive 允许对体积和表面中复杂的空间和反应扩散介导的细胞过程进行模拟和可视化。正如我们所展示的，它有可能提供难以通过实验获得的机制见解。电子补充材料：本文的在线版本 (doi:10.1007/s11693-009-9047-2) 包含补充材料，可供授权用户使用。
UNLABELLED: Many important cellular processes are regulated by reaction-diffusion (RD) of molecules that takes place both in the cytoplasm and on the membrane. To model and analyze such multicompartmental processes, we developed a lattice-based Monte Carlo method, Spatiocyte that supports RD in volume and surface compartments at single molecule resolution. Stochasticity in RD and the excluded volume effect brought by intracellular molecular crowding, both of which can significantly affect RD and thus, cellular processes, are also supported. We verified the method by comparing simulation results of diffusion, irreversible and reversible reactions with the predicted analytical and best available numerical solutions. Moreover, to directly compare the localization patterns of molecules in fluorescence microscopy images with simulation, we devised a visualization method that mimics the microphotography process by showing the trajectory of simulated molecules averaged according to the camera exposure time. In the rod-shaped bacterium Escherichia coli, the division site is suppressed at the cell poles by periodic pole-to-pole oscillations of the Min proteins (MinC, MinD and MinE) arising from carefully orchestrated RD in both cytoplasm and membrane compartments. Using Spatiocyte we could model and reproduce the in vivo MinDE localization dynamics by accounting for the previously reported properties of MinE. Our results suggest that the MinE ring, which is essential in preventing polar septation, is largely composed of MinE that is transiently attached to the membrane independently after recruited by MinD. Overall, Spatiocyte allows simulation and visualization of complex spatial and reaction-diffusion mediated cellular processes in volumes and surfaces. As we showed, it can potentially provide mechanistic insights otherwise difficult to obtain experimentally.ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11693-009-9047-2) contains supplementary material, which is available to authorized users.